Traditional drug discovery involves the screening of lead compounds from a chemical library by using cell-based high throughput screening (HTS) procedures. This has created a demand for the development of cell-based microarray chips for HTS of compounds. Although several cell-based microarray devices and procedures for screening of chemical libraries have been reported, each has limitations in terms of simplicity, speed, and cost. Here, we sought to make a simple method for producing multiple copies of microarray chips for the controlled release of small molecules during cell-based screening...

BACKGROUND: In the estimation of repeat numbers in a short tandem repeat (STR) region from high-throughput sequencing data, two types of strategies are mainly taken: a strategy based on counting repeat patterns included in sequence reads spanning the region and a strategy based on estimating the difference between the actual insert size and the insert size inferred from paired-end reads. The quality of sequence alignment is crucial, especially in the former approaches although usual alignment methods have difficulty in STR regions due to insertions and deletions caused by the variations of repeat numbers...

A Faraday-cup type lost-fast ion probe (FLIP) has been designed and installed in Heliotron J for the purpose of the studies of interaction between fast ions and MHD instabilities. The FLIP can measure the co-going fast ions whose energy is in the range of 1.7-42.5 keV (proton) and pitch angle of 90(∘)-140(∘), especially for fast ions having the injection energy of neutral beam injection (NBI). The FLIP successfully measured the re-entering passing ions and trapped lost-fast ions caused by fast-ion-driven energetic particle modes in NBI heated plasmas...

This paper describes the development study of the beam emission spectroscopy (BES) for the turbulent transport study in Heliotron J. Modification of the sightlines (10 × 4 for edge and 10 × 2 for edge) enables us to obtain 2-dimensional BES imaging. The cooling effect on the reduction in the electrical noise of avalanche photodiode (APD) assembly has been investigated using a refrigerant cooling system. When the temperature of the APD element has set to be -20 °C, the electrical noise can be reduced more than 50%...

Most indigenous citrus varieties are assumed to be natural hybrids, but their parentage has so far been determined in only a few cases because of their wide genetic diversity and the low transferability of DNA markers. Here we infer the parentage of indigenous citrus varieties using simple sequence repeat and indel markers developed from various citrus genome sequence resources. Parentage tests with 122 known hybrids using the selected DNA markers certify their transferability among those hybrids. Identity tests confirm that most variant strains are selected mutants, but we find four types of kunenbo (Citrus nobilis) and three types of tachibana (Citrus tachibana) for which we suggest different origins...

BACKGROUND: Chronic cough involves airway remodeling associated with cough reflex hypersensitivity. Whether cough itself induces these features remains unknown. METHODS: Guinea pigs were assigned to receive treatment with citric acid (CA), saline (SA), or CA+dextromethorphan (DEX). All animals were exposed to 0.5M CA on days 1 and 22. On days 4-20, the CA and CA+DEX groups were exposed to CA, and the SA group to saline thrice weekly, during which the CA+DEX group was administered DEX pretreatment to inhibit cough...

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is considered an alternative marker of eosinophilic airway inflammation and is sometimes incorporated in the diagnosis of asthma. However, many patients with cough variant asthma (CVA) demonstrate an FeNO in the normal range. Therefore, additional information is needed to confirm the diagnosis of CVA, particularly in patients with low FeNO levels. We aimed to investigate the feasibility of using cough triggers to help diagnose CVA. METHODS: We studied 163 patients presenting with prolonged/chronic cough alone (including 104 CVA patients) who underwent FeNO measurements and an airway responsiveness test, and answered a questionnaire listing 18 cough triggers...

Tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine biosynthesis, and its stability is a fundamental factor to maintain the level of the catecholamines in cells. However, the intracellular stability of TH determined by the degradation remains unknown; although the TH molecule phosphorylated at its Ser19 was observed in the nucleus, and the phosphorylation suspected to trigger its proteasome-mediated degradation. Computer-assisted analysis using the cNLS Mapper program predicted that two sequences of nuclear localization signals (NLS) exist in the N-terminus of TH molecule containing the phosphorylation sites Ser19, Ser31, and Ser40 (Pro(9)-Arg(38) and Lys(12)-Ile(42)): the NLS scores indicated that TH could become localized in both nucleus and cytoplasm...

BACKGROUND/AIMS: A high expression of Wilms tumor 1 (WT1) mRNA occurs in most cases of acute leukemia and myelodysplastic syndrome (MDS). Although there are many reports suggesting that acute myeloid leukemia patients with high expression levels of WT1 mRNA have a relatively poor long-term survival, there are few reports addressing the relationship between WT1 levels and prognosis in MDS. METHODS: We retrospectively analyzed 42 elderly patients with MDS whose WT1 levels at diagnosis were available, and we assessed the relationships between WT1 levels in peripheral blood and preexisting prognostic factors such as World Health Organization prognostic scores and Revised International Prognostic Scoring System risk categories, bone marrow blast percentages, and chromosomal abnormalities linked to a poor prognosis...

Getah virus (GETV; genus Alphavirus, family Togaviridae) is a mosquito-borne virus known to cause disease in horses and pigs. In 2014, for the first time in ∼30 years, a sudden GETV outbreak occurred among racehorses in Ibaraki, Japan. Two years before this outbreak, we obtained multiple GETV isolates from Culex tritaeniorhynchus mosquitoes collected in Nagasaki, Japan and determined the whole genome sequence of GETV isolate 12IH26. Our phylogenetic analysis of GETV strains revealed that the isolate 12IH26 forms a robust clade with the epidemic strains 14-I-605-C1 and 14-I-605-C2 isolated from horses in the 2014 outbreak in Ibaraki...

Arylboronate esters bearing methyl groups in both of their ortho positions were stably incorporated into lipid membranes at high concentrations without undergoing hydrolysis to the corresponding boronic acids. This method could be used in combination with previous methods to increase the maximum ratio of boron atoms in liposomal boron carriers.

GPR142 is a G-protein-coupled receptor (GPCR), whose most potent and efficacious ligand has been reported as being the natural amino acid l-tryptophan. GPR142 is highly expressed in pancreatic β-cells and immune cells, suggesting the receptor may play a role in the pathogenesis and development of diabetes or inflammatory diseases. In a previous report, we developed GPR142 agonists as insulin secretagogues. In this report, we show the discovery of a selective, potent small-molecule GPR142 antagonist, CLP-3094, and its pharmacological characteristics...

An injection barrel was designed and fabricated for a small size 0.8 mm cryogenic pellet with a low speed of 200-300 m/s in medium-sized plasma fusion devices. Pellet injection with pneumatic acceleration was examined using a conventional in situ technique. A tapered structure was applied in the downstream side of the injection barrel to satisfy the requirement of pellet speed reduction by expansion of the propellant gas. Shadowgraph and light gate measurements show that the intact pellets have speeds of 260 ± 30 m/s and a typical size of 1...

BACKGROUND: Ticks have been long known as vectors of various pathogens, some of which can cause high fatality rates among infected individuals. Our enhanced tick surveillance around Nagasaki, Japan, led to the isolation and identification of a new strain of a recently identified Orbivirus, Muko virus (MUV). The orbiviruses have a wide host range, including humans, and is related to a spectrum of clinical outcomes. However, the zoonotic potential of some members of the genus, although reported, were not clearly elucidated...

A chemical synthesis of a core fucose containing N-glycan was achieved. The asparagine was introduced at the early-stage of the synthesis and the sugar chain was convergently elongated. As for the fragment synthesis, we reinvestigated alpha-sialylation, beta-mannosylation, and N-glycosylation to reveal that precise temperature control was essential for these glycosylations. Intermolecular hydrogen bonds involving acetamide groups were found to reduce the reactivity in glycosylations: the protection of NHAc as NAc2 dramatically improved the reactivity...

Heavy meromyosin (HMM) of myosin II and cofilin each binds to actin filaments cooperatively and forms clusters along the filaments, but it is unknown whether the two cooperative bindings are correlated and what physiological roles they have. Fluorescence microscopy demonstrated that HMM-GFP and cofilin-mCherry each bound cooperatively to different parts of actin filaments when they were added simultaneously in 0.2 μM ATP, indicating that the two cooperative bindings are mutually exclusive. In 0.1 mM ATP, the motor domain of myosin (S1) strongly inhibited the formation of cofilin clusters along actin filaments...

BACKGROUND: For patients with low-lying rectal cancer, the feasibility of anus-preserving surgery in combination with neoadjuvant chemoradiotherapy (NACRT) has been not well established from the perspective of patient-centered outcomes. METHODS: We investigated 278 patients with low-lying rectal adenocarcinoma from 2005 to 2012. We compared their symptoms and QOL scores of patients who underwent anus-preserving surgery with (n = 88) and without (n = 143) NACRT according to the Wexner scale, EORTC QLQ C-30, CR29, and the modified fecal incontinence quality life scale (mFIQL)...